Michael Varenbut

Screening for Substance Use Patterns among Patients Referred for a Variety of Sleep Complaints

Virtually all psychiatric and substance use disorders are associated with sleep disruption. Studies indicate that psychiatric disorders are related closely to chronic insomnia and that psychoactive substances have acute and chronic effects on sleep architecture. Several aspects of sleep are compromised in individuals taking these substances, ranging from difficulty initiating sleep to difficulty maintaining sleep and hypersomnia. Sleep disturbances are apparent in person taking psychoactive drugs or alcohol and have been found to persist long after withdrawing from these drugs. For some, sleep disturbance can be so severe as to reverse treatment success and precipitate relapse to addiction or dependence. There is increasing evidence that primary insomnia without a concurrent psychiatric disorder is a risk factor for later developing substance use disorders. Patients were asked to complete two brief screening tools, the Michigan Alcohol Screening Test and Drug Abuse Screening Test, to examine substance use patterns among patients referred for a variety of sleep complaints in a sleep disorders clinic. We found that patients who demonstrated a variety of sleep complaints were more likely to have alcohol and drug problems than those in the general populations.

A psychometric study of the prevalence of DSM-IV personality disorders among office-based methadone maintenance patients.

Using the DSM‐IV criteria for personality disorders, prevalence rates for these disorders were evaluated among methadone maintenance patients, with a psychometric test—the Millon Clinical Multiaxial Inventory (MCMI‐III). We found that 77% of patients met the study criteria for at least one personality disorder. Of those who had a personality disorder, 20% had two personality disorders, 14% had three personality disorders, and 6% had four personality disorders. Rates of specific personality disorders are reported. Consistencies and divergence from existing research literature are noted. It is suggested that future research compare psychometrically based self‐report questionnaires to a structured clinical interview format, within the same clinical population.

Testosterone suppression in opioid users: A systematic review and meta-analysis ☆

BACKGROUND Whether used for pain management or recreation, opioids have a number of adverse effects including hormonal imbalances. These imbalances have been reported to primarily involve testosterone and affect both males and females to the point of interfering with successful treatment and recovery. We conducted a systematic review and meta-analysis to determine the extent that opioids affect testosterone levels in both men and women, which may be relevant to improved treatment outcomes for opioid dependence and for pain management. METHODS We searched PubMed, EMBASE, PsycINFO, and CINAHL for relevant articles and included studies that examined testosterone levels in men and women while on opioids. Data collection was completed in duplicate. RESULTS Seventeen studies with 2769 participants (800 opioid users and 1969 controls) fulfilled the review inclusion criteria; 10 studies were cross-sectional and seven were cohort studies. Results showed a significant difference in mean testosterone level in men with opioid use compared to controls (MD=-164.78; 95% CI: -245.47, -84.08; p<0.0001). Methadone did not affect testosterone differently than other opioids. Testosterone levels in women were not affected by opioids. Generalizability of results was limited due to high heterogeneity among studies and overall low quality of evidence. CONCLUSIONS Our findings demonstrated that testosterone level is suppressed in men with regular opioid use regardless of opioid type. We found that opioids affect testosterone levels differently in men than women. This suggests that opioids, including methadone, may have different endocrine disruption mechanisms in men and women, which should be considered when treating opioid dependence.

Screening for Alcohol Use Patterns Among Methadone Maintenance Patients

Alcohol use among Methadone Maintenance Treatment (MMT) patients poses a major health risk, exacerbates psychopathology, and increases the risk of death by accidental overdose. Despite these factors, screening for alcohol use remains underutilized in the methadone community. Utilizing a self-report screening measure—the Michigan Alcohol Screening Test (MAST)—and consistent with the literature, we found high rates of alcohol problems among MMT patients. Benefits and limitations of using the MAST to screen for alcohol use patterns are discussed.

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

BackgroundOpioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence.Methods/DesignThe authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse).DiscussionUsing evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine.Systematic review registrationPROSPERO CRD42013006507.

Methadone induces testosterone suppression in patients with opioid addiction

Sex hormones may have a role in the pathophysiology of substance use disorders, as demonstrated by the association between testosterone and addictive behaviour in opioid dependence. Although opioid use has been found to suppress testosterone levels in men and women, the extent of this effect and how it relates to methadone treatment for opioid dependence is unclear. The present multi-centre cross-sectional study consecutively recruited 231 patients with opioid dependence from methadone clinics across Ontario, Canada between June and December of 2011. We obtained demographic details, substance use, psychiatric history, and blood and urine samples from enrolled subjects. The control group included 783 non-opioid using adults recruited from a primary care setting in Ontario, Canada. Average testosterone level in men receiving methadone treatment was significantly lower than controls. No effect of opioids including methadone on testosterone level in women was found and testosterone did not fluctuate significantly between menstrual cycle phases. In methadone patients, testosterone level was significantly associated with methadone dose in men only. We recommend that testosterone levels be checked in men prior and during methadone and other opioid therapy, in order to detect and treat testosterone deficiency associated with opioids and lead to successful methadone treatment outcomes.

Genetic influence on methadone treatment outcomes in patients undergoing methadone maintenance treatment for opioid addiction: a pilot study

Introduction Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population. Methods This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes. Results The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and medical comorbidities. BDNF rs6265 and DRD2 rs1799978 were the common single nucleotide polymorphisms (SNPs) selected for the feasibility study. Discussion This study met our predetermined feasibility criteria; recruitment, response rates, and genetic testing were feasible; treatment duration was sufficient for follow up; and the prevalence of comorbid conditions indicated the need for reliable psychiatric and chronic pain measures. The study strengths included effective collaboration with clinics and the generalizability of sample population. Key learning points show the need for assessment of treatment outcomes on multiple domains, implementation of follow up, and the development of standardized training for the study clinical staff.

Tampering by office-based methadone maintenance patients with methadone take home privileges: a pilot study

Methadone Maintenance Treatment (MMT) is among the most widely studied treatments for opiate dependence with proven benefits for patients and society. When misused, however, methadone can also be lethal. The issue of methadone diversion is a major concern for all MMT programs. A potential source for such diversion is from those MMT patients who receive daily take home methadone doses. Using a reverse phase high performance liquid chromatography method, seven of the nine patients who were randomly selected to have all of their remaining methadone take home doses (within a 24 hour period) analyzed, returned lower than expected quantities of methadone. This finding suggests the possibility that such patients may have tampered with their daily take home doses. Larger prospective observational studies are clearly needed to test the supposition of this pilot study.

Evaluation of clinical and inflammatory profile in opioid addiction patients with comorbid pain: results from a multicenter investigation

Background Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT), with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population. Methods The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235) on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and chemokine (C–C motif) ligand 2 [CCL2]). The study objectives were addressed using a descriptive statistical summary and a multivariable logistic regression model constructed in STATA version 12. Results Among the participants eligible for inclusion (n=235), serum IFN-γ level and substance abuse behavior proved to be important delineating characteristics for the detection of comorbid pain. Analysis of inflammatory profile showed IFN-γ to be significantly elevated among patients reporting comorbid pain (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.17, 3.50; P=0.01). Patients reporting comorbid pain were also found to have an increase in positive opioid urine screens (OR: 1.02; 95% CI: 1.00, 1.03; P=0.01), indicating an increase in illicit opioid consumption. Conclusion MMT patients with comorbid pain were shown to have elevated IFN-γ and higher rates of continued opioid abuse. The ability to objectively distinguish between patients with comorbid pain may help to both improve the prediction of poor responders to MMT as well as identify treatment approaches such as anti-inflammatory medications as safe alternatives for MMT patients with comorbid pain.

The effectiveness of telemedicine-delivered opioid agonist therapy in a supervised clinical setting

OBJECTIVE Opioid use disorder has been declared a public health crisis across North America and opioid agonist therapy (OAT) is the standard of care for these patients. Despite the increasing adoption of telemedicine as a delivery method for OAT, its effectiveness has not yet been evaluated against traditional in-person treatment. This study compared treatment outcomes for in-person versus telemedicine-delivered OAT. METHODS We conducted a non-randomized cohort comparison study using an administrative database for patients who commenced OAT between 2011 and 2012 across 58 clinic sites in the province of Ontario, Canada. Patients were stratified by primary treatment modality as being: in-person (<25% appointments by telemedicine), mixed (25-75% by telemedicine), or via telemedicine (>75% appointments by telemedicine). The primary outcome was continuous retention in treatment as defined by one year of uninterrupted therapy, based on pharmacy dosing records. RESULTS A total of 3733 OAT initiating patients were identified. Patients treated via telemedicine were more likely to be retained in therapy than patients treated in-person (n=1590; aOR=1.27; 95% CI 1.14-1.41; p<0.001). Telemedicine patients demonstrated a retention rate of 50% at one year whereas in-person patients were retained at a rate of 39%. The mixed group also had higher likelihood of retention than the in-person group (n=418; aOR=1.26; 95% CI 1.08-1.47; p=0.001) and had a retention rate of 47% at one year. CONCLUSION Telemedicine may be an effective alternative to delivering in person OAT, and it has the potential to expand access to care in rural, remote, and urban regions.